Journal
CEREBROVASCULAR DISEASES
Volume 25, Issue 4, Pages 338-343Publisher
KARGER
DOI: 10.1159/000118379
Keywords
ischemic stroke; thrombolysis; blood brain barrier; mechanical embolectomy; MRI
Categories
Funding
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB002087] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [K24NS002092, Z01NS003044, K23NS002088, Z01NS003043, R01NS039498, Z01NS003045] Funding Source: NIH RePORTER
- Intramural NIH HHS [ZIA NS003043-10] Funding Source: Medline
- NIBIB NIH HHS [EB 002087] Funding Source: Medline
- NINDS NIH HHS [NS 39498, K24 NS 02092, K23 NS 02088] Funding Source: Medline
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Background: In experimental models of cerebral ischemia, thrombolytic drugs have been demonstrated to have a number of neurovascular toxic effects including blood brain barrier disruption. Early barrier opening caused by focal cerebral ischemia in human stroke can be assessed by the presence of gadolinium enhancement of cerebrospinal fluid, termed 'Hyperintense Acute Injury Marker' (HARM). Methods: In a retrospective analysis, the frequency of HARM was studied in 140 patients, 38 receiving intra-arterial thrombolytics, 18 undergoing mechanical embolectomy, 24 receiving intravenous tissue plasminogen activator and 60 patients receiving no acute intervention. Results: HARM was found in 66% of patients undergoing intra-arterial thrombolysis and 50% of patients receiving intravenous tissue plasminogen activator, compared to 28% of patients undergoing mechanical embolectomy and 30% of patients receiving no acute therapy (p = 0.002). Both thrombolytic therapy (p = 0.001) and age (p = 0.001) were independent predictors of HARM. HARM was an independent predictor of hemorrhagic transformation (p = 0.007). Conclusions: This is the first study in humans providing supportive evidence of the neurovascular toxic effects of thrombolytics and suggests that HARM may be used as a biomarker of blood brain barrier disruption in future research of acute stroke therapies. Copyright (C) 2008 S. Karger AG, Basel.
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